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FOXA1.txt
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1. Mol Cell. 2024 Jan 18;84(2):244-260.e7. doi: 10.1016/j.molcel.2023.11.020. Epub
2023 Dec 14.
FOXA1 forms biomolecular condensates that unpack condensed chromatin to function
as a pioneer factor.
Ji D(1), Shao C(1), Yu J(2), Hou Y(3), Gao X(1), Wu Y(1), Wang L(4), Chen P(5).
Author information:
(1)Department of Immunology, School of Basic Medical Sciences, Beijing Key
Laboratory for Tumor Invasion and Metastasis, Capital Medical University,
Beijing 100069, China.
(2)National Laboratory of Biomacromolecules, CAS Center for Excellence in
Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing
100101, China.
(3)National Laboratory of Biomacromolecules, CAS Center for Excellence in
Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing
100101, China; Hubei Key Laboratory of Genetic Regulation and Integrative
Biology, School of Life Sciences, Central China Normal University, Wuhan 430079,
China.
(4)National Laboratory of Biomacromolecules, CAS Center for Excellence in
Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing
100101, China; Beijing Frontier Research Center for Biological Structure, School
of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic
address: [email protected].
(5)Department of Immunology, School of Basic Medical Sciences, Beijing Key
Laboratory for Tumor Invasion and Metastasis, Capital Medical University,
Beijing 100069, China; National Laboratory of Biomacromolecules, CAS Center for
Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of
Sciences, Beijing 100101, China. Electronic address: [email protected].
Eukaryotic DNA is packaged into chromatin in the nucleus, restricting the
binding of transcription factors (TFs) to their target DNA sites. FOXA1
functions as a pioneer TF to bind condensed chromatin and initiate the opening
of local chromatin for gene expression. However, the principles of FOXA1
recruitment and how it subsequently unpacks the condensed chromatin remain
elusive. Here, we revealed that FOXA1 intrinsically forms submicron-sized
condensates through its N- and C-terminal intrinsically disordered regions
(IDRs). Notably, both IDRs enable FOXA1 to dissolve the condensed chromatin. In
addition, the DNA-binding capacity of FOXA1 contributes to its ability to both
form condensates and dissolve condensed chromatin. Further genome-wide
investigation showed that IDRs enable FOXA1 to bind and unpack the condensed
chromatin to regulate the proliferation and migration of breast cancer cells.
This work provides a principle of how pioneer TFs function to initiate competent
chromatin states using their IDRs.
Copyright © 2023 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.molcel.2023.11.020
PMID: 38101414 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of interests The authors declare no
competing interests.